Covid19
Conditions
Keywords
SARS-CoV-2, Covid, Covid19 Diarrhea, Covid19 GI Infection
Brief summary
This is a 2-part, 2-arm, Phase 2 , multicentre, randomized, double-blind, placebo-controlled study in adults with COVID-19 with gastrointestinal infection.
Interventions
DRUGNiclosamide
Niclosamide tablets 400 mg 3 times daily for 14 days
DRUGPlacebo
Matched placebo tablets 400 mg 3 times daily for 14 days
Sponsors
Entero Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Part 1 only, patients with a primary diagnosis of COVID-19, with or without pneumonia, who agree to be monitored daily for at least 7 days after randomization and who accept continuing to be assessed for the study procedures. 2. Part 2 only, patients with a primary diagnosis of COVID-19, with or without pneumonia.
Exclusion criteria
1. At the time of randomization, patients who require intensive care unit (ICU) admission or patients with severe respiratory insufficiency who require mechanical ventilation or with rapid worsening of respiratory function leading to expectation for mechanical ventilation or ICU admission. 2. Evidence of rapid clinical deterioration or existence of any life-threatening co-morbidity or any other medical condition that, in the opinion of the investigator, makes the patient unsuitable for inclusion. 3. Patients who, at the time of enrollment, are not in a clinical condition compatible with the oral administration of the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SAEs | Day 1 to 6 weeks | Serious adverse event (SAE) coded by System Organ Class (SOC) and Preferred Term (PT), using the Medical Dictionary for Regulatory Activities (MedDRA). |
| TEAE | Day 1 to 6 weeks | Proportion of patients with Treatment Emergent Adverse Events (TEAE) leading to study drug discontinuation. |
| Fecal RNA Virus Clearance | Day 1 to 6 weeks | Time to fecal viral RNA clearance (stool sample) assessed by RT-qPCR in the niclosamide arm compared to the placebo arm. |
| Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Leukocytes and Platelets) | Day 1 to Day 43 | Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. |
| Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Erythrocytes) | Day 1 to Day 43 | Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. Erythrocytes |
| Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Hemocrit) | Day 1 to Day 43 | Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. Hemocrit (L/L) |
| Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Hemoglobin) | Day 1 to Day 43 | Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. Hemoglobin (g/L) |
| Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Corpuscular Volume) | Day 1 to Day 43 | Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. Corpuscular volume (fL) |
| Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium) | Day 1 to Day 43 | Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. |
| Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Alkaline Phosphatase, AST, ALT, and LDH) | Day 1 to Day 43 | Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. |
| Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Bilirubin and Serum Creatinine) | Day 1 to Day 43 | Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. |
Countries
India, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Niclosamide Niclosamide tablets 400 mg 3 times daily for 14 days
Niclosamide: Niclosamide tablets 400 mg 3 times daily for 14 days | 84 |
| Placebo Matching placebo tablets 3 times daily for 14 days
Placebo: Matched placebo tablets 400 mg 3 times daily for 14 days | 82 |
| Total | 166 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Niclosamide | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 8 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 77 Participants | 74 Participants | 151 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 55 Participants | 63 Participants | 118 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 19 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 5 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 71 Participants | 74 Participants | 145 Participants |
| Sex: Female, Male Female | 47 Participants | 46 Participants | 93 Participants |
| Sex: Female, Male Male | 37 Participants | 36 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 82 |
| other Total, other adverse events | 1 / 84 | 1 / 82 |
| serious Total, serious adverse events | 0 / 84 | 2 / 82 |
Outcome results
Primary
Fecal RNA Virus Clearance
Time to fecal viral RNA clearance (stool sample) assessed by RT-qPCR in the niclosamide arm compared to the placebo arm.
Time frame: Day 1 to 6 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Niclosamide | Fecal RNA Virus Clearance | Day 22 | 48 participants |
| Niclosamide | Fecal RNA Virus Clearance | Day 4 | 8 participants |
| Niclosamide | Fecal RNA Virus Clearance | Day 29 | 51 participants |
| Niclosamide | Fecal RNA Virus Clearance | Day 15 | 40 participants |
| Niclosamide | Fecal RNA Virus Clearance | Day 36 | 51 participants |
| Niclosamide | Fecal RNA Virus Clearance | Day 43 | 52 participants |
| Niclosamide | Fecal RNA Virus Clearance | Day 8 | 21 participants |
| Placebo | Fecal RNA Virus Clearance | Day 43 | 48 participants |
| Placebo | Fecal RNA Virus Clearance | Day 4 | 9 participants |
| Placebo | Fecal RNA Virus Clearance | Day 8 | 20 participants |
| Placebo | Fecal RNA Virus Clearance | Day 15 | 33 participants |
| Placebo | Fecal RNA Virus Clearance | Day 22 | 42 participants |
| Placebo | Fecal RNA Virus Clearance | Day 29 | 43 participants |
| Placebo | Fecal RNA Virus Clearance | Day 36 | 45 participants |
Primary
SAEs
Serious adverse event (SAE) coded by System Organ Class (SOC) and Preferred Term (PT), using the Medical Dictionary for Regulatory Activities (MedDRA).
Time frame: Day 1 to 6 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Niclosamide | SAEs | Infections and infestations | 0 participants |
| Niclosamide | SAEs | Injury, poisoning and procedural complications | 0 participants |
| Placebo | SAEs | Infections and infestations | 1 participants |
| Placebo | SAEs | Injury, poisoning and procedural complications | 1 participants |
Primary
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Alkaline Phosphatase, AST, ALT, and LDH)
Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided.
Time frame: Day 1 to Day 43
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Alkaline Phosphatase, AST, ALT, and LDH) | AST | -2.5 U/L |
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Alkaline Phosphatase, AST, ALT, and LDH) | Alkaline Phosphatase | 2.0 U/L |
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Alkaline Phosphatase, AST, ALT, and LDH) | ALT | -3.0 U/L |
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Alkaline Phosphatase, AST, ALT, and LDH) | LDH | -2.0 U/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Alkaline Phosphatase, AST, ALT, and LDH) | LDH | 6.0 U/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Alkaline Phosphatase, AST, ALT, and LDH) | ALT | -4.0 U/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Alkaline Phosphatase, AST, ALT, and LDH) | Alkaline Phosphatase | 2.0 U/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Alkaline Phosphatase, AST, ALT, and LDH) | AST | -1.0 U/L |
Primary
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Bilirubin and Serum Creatinine)
Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided.
Time frame: Day 1 to Day 43
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Bilirubin and Serum Creatinine) | Bilirubin | 0.60 mcmol/L |
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Bilirubin and Serum Creatinine) | Creatinine | 0.0 mcmol/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Bilirubin and Serum Creatinine) | Bilirubin | 1.20 mcmol/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Bilirubin and Serum Creatinine) | Creatinine | 0.0 mcmol/L |
Primary
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium)
Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided.
Time frame: Day 1 to Day 43
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium) | Chloride | 2.0 mmol/L |
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium) | BUN | 0.000 mmol/L |
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium) | Potassium | 0.00 mmol/L |
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium) | Sodium | 1.0 mmol/L |
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium) | Glucose | -0.360 mmol/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium) | Sodium | 0.0 mmol/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium) | Glucose | 0.110 mmol/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium) | Chloride | 1.0 mmol/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium) | Potassium | 0.10 mmol/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium) | BUN | 0.000 mmol/L |
Primary
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Corpuscular Volume)
Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. Corpuscular volume (fL)
Time frame: Day 1 to Day 43
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Corpuscular Volume) | -0.35 fL |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Corpuscular Volume) | -0.75 fL |
Primary
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Erythrocytes)
Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. Erythrocytes
Time frame: Day 1 to Day 43
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Erythrocytes) | -0.250 cells 10^12/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Erythrocytes) | -0.125 cells 10^12/L |
Primary
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Hemocrit)
Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. Hemocrit (L/L)
Time frame: Day 1 to Day 43
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Hemocrit) | -0.0195 L/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Hemocrit) | -0.0130 L/L |
Primary
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Hemoglobin)
Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. Hemoglobin (g/L)
Time frame: Day 1 to Day 43
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Hemoglobin) | -4.0 g/L |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Hemoglobin) | -2.5 g/L |
Primary
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Leukocytes and Platelets)
Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided.
Time frame: Day 1 to Day 43
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Leukocytes and Platelets) | Leukocytes | 0.340 cells (10^9/L) |
| Niclosamide | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Leukocytes and Platelets) | Platelets | 11.5 cells (10^9/L) |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Leukocytes and Platelets) | Leukocytes | 0.495 cells (10^9/L) |
| Placebo | Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Leukocytes and Platelets) | Platelets | 3.0 cells (10^9/L) |
Primary
TEAE
Proportion of patients with Treatment Emergent Adverse Events (TEAE) leading to study drug discontinuation.
Time frame: Day 1 to 6 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Niclosamide | TEAE | Musculoskeletal and connective tissue disorders | 0 participants |
| Niclosamide | TEAE | Gastrointetinal disorders | 1 participants |
| Niclosamide | TEAE | Blood and lymphatic system disorders | 0 participants |
| Niclosamide | TEAE | Endocrine disorders | 0 participants |
| Niclosamide | TEAE | Infections and infestations | 0 participants |
| Niclosamide | TEAE | Injury, poisoning and procedural complications | 0 participants |
| Niclosamide | TEAE | Investigations | 1 participants |
| Placebo | TEAE | Musculoskeletal and connective tissue disorders | 1 participants |
| Placebo | TEAE | Infections and infestations | 1 participants |
| Placebo | TEAE | Gastrointetinal disorders | 1 participants |
| Placebo | TEAE | Investigations | 1 participants |
| Placebo | TEAE | Blood and lymphatic system disorders | 1 participants |
| Placebo | TEAE | Injury, poisoning and procedural complications | 1 participants |
| Placebo | TEAE | Endocrine disorders | 1 participants |